Project Summary Developmental Core A major challenge to children's environmental health research is capturing the dynamic nature of environment, particularly how to capture it retrospectively. The lack of advanced exposure tools to address exposure timing limits research on critical windows of susceptibility ? life stages when individuals are highly vulnerable to environmental exposures. Prospective birth cohorts may capture these relationships, but are expensive both in time and money. The absence of objective retrospective biomarkers that provide information on both the magnitude and timing of fetal and early childhood exposure to multiple chemicals is a major barrier in environmental epidemiology. The primary mission of the Developmental Core is to develop, validate and standardize precise, unbiased, retrospective biomarkers of multi-chemical exposures at specific life stages including prenatal life, effectively providing data equivalent to a prospective longitudinal design. A major focus will be retrospective exposure reconstruction biomarkers that objectively measure prenatal and infant environment, even when samples are collected during childhood or adolescence. These will include tooth matrix-based biomarkers that exploit dentine growth rings to reconstruct the timing and dose of toxic/nutrient elements and organic chemical exposures in fetal life and infancy. We will also develop dental matrix based untargeted assays to create a `retrospective dynamic exposome' biomarker. In parallel, we will also develop methods to estimate embryonic and early fetal exposure using innovative assays of hair collected from pregnant women to reconstruct temporal periconceptual chemical exposures. It is now recognized that tissue architecture must be considered during any chemical analyses for exposure assessment. Our Core will apply multidimensional (2D and 3D) tissue bio-imaging that quantifies the spatial distribution of both metals and biomolecules within tissue sections using high-resolution laser-based mass spectrometry combined with multiplexed metal-tagged immunolabelling. We will also develop metalloproteomic techniques that can investigate metal-toxin metabolism and its effects on normal metal homeostasis. Finally, the Core Co-Leader (Baccarelli) is a renowned expert in environmental epigenetics and will develop novel biological response biomarkers that address the DNA conformational states that arise from DNA methylation and histone modifications. He will also work jointly with Core Leader (Arora) on measuring miRNA and mtDNA biomarkers in hair that can recapitulate past biological response to the environment, thereby complementing Dr. Arora's work on laser ablation ICP-MS and hair metals. The Developmental Core will integrate with the other Resources, so that our work can be incorporated as services offered by the three Hub Resources. This will be accomplished through shared personnel, resources and the monthly Executive Steering Committee meetings. Our goal is to bring new biomarkers into the CHEAR network as fully developed, high-throughput platforms.